This invention relates to a method and compositions useful in treating both internal and external eye inflammations. Specifically, this invention relates to methods and compositions which use certain nonsteroidal anti-inflammatory drugs to control internal and external eye inflammation.
For over a decade nonsteroidal anti-inflammatory drugs have been tested for their ability to suppress corneal inflammations. Indomethacin, fenoprofen, oxyphenbutazone, suprofen, and flurbiprofen were found to be effective in the laboratory and in the clinic for treating postoperative corneal inflammations. When compared to the commercially available topical corticosteroids, the nonsteroidal anti-inflammatory drugs are not as effective in treating corneal inflammations. Also, the currently available nonsteroidal anti-inflammatory drugs appear to have very little usefulness in clinically treating inflammations of the anterior chamber.
The nonsteroidal anti-inflammatory drugs were designed for systemic use and not for topical application to the eye. However, the requirements for optimal pharmacokinetics in the eye are quite different when compared to the systemic route of administration. An additional limitation to use of nonsteroids for ophthalmic use is their intrinsic pharmacological activity, which has been shown to be lower than the corticosteroids. These factors make it important to design molecules specially for the eye if topical application of nonsteroids is to be successful.
An object of this invention is to improve corneal penetration and most importantly, to improve distribution to and retention within, the iris/ciliary body tissue of nonsteroid drugs for inflammation treatment. Topical therapy using nonsteroidal anti-inflammatory drugs for corneal and anterior chamber inflammations would be very advantageous compared to the use of the corticosteroids. Steroids are responsible for various unwanted side effects, such as, an increase in intraocular pressure, delayed wound healing, cataract formation and corneal perforation.
As earlier stated, most inflammations of the eye are currently treated by other steroids which penetrate the eye and work effectively, but cause undesirable side effects. The undesirable side effects referred to earlier are exemplified by increased intraocular pressure, delayed wound healing, cataract formation and corneal perforations. On the other hand, if steroids are replaced with nonsteroidal anti-inflammatory drugs which do not penetrate the eye in therapeutic concentrations, they are generally effective only for external inflammations and thus have limited therapeutic application, i.e. pre-surgery. It thus can be seen that a continuing need exists for a drug which would both penetrate and be effective for not only external, but internal eye inflammations, and at the same time be free of systemic side effects.
The primary objective of the present invention is then to provide a nonsteroidal anti-inflammatory drug which will effectively penetrate the eye in therapeutic concentrations, which is effective for both internal and external inflammations, and which does not cause the typical systemic side effects of steroidal anti-inflammatory drugs.
Another objective of the present invention is to provide drugs which do not have one typical undesirable side effect of Ibuprofen, i.e. ulcer causation.